Game-Changers 2015: Refining Treatment in Arthritis

In RA, more JAK inhibitors coming; in PsA, targeting IL-17

Widening experience with JAK inhibition for rheumatoid arthritis (RA) and tapering medications among RA patients in remission, along with the success of secukinumab for psoriatic arthritis (PsA), were the most important advances in rheumatology in 2015, according to specialists responding to MedPage Today.

We contacted 13 rheumatologists to ask what they thought were the most significant developments -- the "game-changers" -- in the specialty during 2015.

However, while "baricitinib in RA looks exciting," the data have not yet been published in full, noted Iain McInnes, MD, PhD, of the University of Glasgow.

Other JAK inhibitors that also are "big stories" include ABT-494 and filgotinib, according to Joel Kremer, MD, of the Center for Rheumatology in Albany.

Successful phase II results of the BALANCE trials of ABT-494 were recently announced, and phase IIb trials of filgotinib presented at the ACR meeting showed efficacy for this JAK 1 inhibitor as monotherapy or in combination with methotrexate in RA.

The 2015 ACR guidelines for RA treatment also addressed the possibility of cutting down on medications for patients who are in remission.

"We see that it is possible for some patients to taper their disease modifying agents, as patients are today more likely to be in remission or have low disease activity than in the past," commented Eric Matteson, MD, who chairs the rheumatology department at the Mayo Clinic in Rochester, Minn.

"In some patients receiving a combination of a biological agent (anti-TNF) and methotrexate, a good response can be maintained even with a change in the anti-TNF therapy, either a decreased dose or a complete cessation," said David S. Pisetsky, MD, PhD, of Duke University in Durham, N.C.

"These findings are important in simplifying therapy in some patients and can lead to cost-saving, but further studies are needed to determine whether this approach leads to relapses or effects on the development of later complications," Pisetsky said.

Matteson also pointed out that "the cardiovascular disease burden of RA may be lessening due to improved treatments. A study showed that mortality from cardiovascular disease is approaching that of the general population," he said.

In addition, there have been improvements and advances in technology that may improve RA care, according to Robert Keenan, MD, of Duke University.

These technological advances "are allowing genomic researchers to sequence and analyze genetic data like never before that could lead to a better understanding and additional, possibly more tailored treatment in RA and other autoimmune diseases," Keenan predicted.

Secukinumab a Game-Changer in PsA

For psoriatic arthritis, considerable enthusiasm was in evidence among experts about the interleukin (IL)-17 inhibitor secukinumab.

"We have seen this year breakthrough trials showing a strong effect of secukinumab in psoriasis, psoriatic arthritis, and [we also are] expecting impressive effects in ankylosing spondylitis," said Francis Berenbaum, MD, PhD, of Sorbonne University in Paris.

One of these trials, FUTURE 2, found that the odds ratio of having an ACR20 response at week 24 was 6.81 (95% CI 3.42-13.56) for secukinumab, 300 mg/week versus placebo. This was a highlight of the year, according to Philip Helliwell, MD, of the University of Leeds in England.

That study and another phase II trial "will have significant impact," stated Philip Mease, MD, of the Swedish Medical Center in Seattle.

"IL-17 inhibition is demonstrating similar efficacy in the various clinical domains of psoriatic arthritis as have the TNF inhibitors, including inhibition of radiologic progression, so we will now have (expected approval by mid-2016) a substantive alternative for those who either do not respond to, lose response to, or have intolerability for anti-TNFs," Mease said.

"The arrival of the IL-17 targeted drug secukinumab will dramatically impact patients with cutaneous psoriasis and will be a fabulous addition to the therapeutic arsenal for those with psoriatic arthritis and ankylosing spondylitis," said John J. Cush, MD, of Baylor Research Institute in Dallas.

Secukinumab has already been approved for those two conditions in Europe, Cush added.

Another important advance in rheumatology was the finding that multi-targeted therapy that combined mycophenolate mofetil (Cellcept) with tacrolimus was effective for nephritis in patients with systemic lupus erythematosis. This "provides patients another option for management of one of the more serious manifestations of the illness," commented H. Michael Belmont, MD, of NYU Langone Medical Center in New York City.

There also were major advances in the treatment of systemic sclerosis, according to Daniel Furst, MD, of the University of California Los Angeles. For example, in a phase II study presented at the annual meeting of the European League Against Rheumatism in June, there were "strong trends to efficacy in both the skin and lungs," according to Furst, who was one of the study investigators.

And in another study, mycophenolate was found to be equivalent to oral cyclophosphamide for systemic sclerosis, with slightly less toxicity, Furst noted.

Changes also may be in the wings for the treatment of giant cell arteritis, according to Matteson. "We saw a report that abatacept [Orencia] may be helpful in the management of giant cell arteritis," he said.

IL-6 antagonists also are being investigated for this vasculitis, and "may have important influence on how rheumatologists treat this disease in the future," Matteson commented.

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